title: Paraoxonase 1 (PON1) gene-108C>T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia.
abstract: Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland. makaruk@ipin.edu.pl
authors.forename: Małgorzata Ewa
authors.initials: ME
authors.lastname: Bednarska-Makaruk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Krzywkowski
authors.forename: Alla
authors.initials: A
authors.lastname: Graban
authors.forename: Wanda
authors.initials: W
authors.lastname: Lipczyńska-Łojkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Bochyńska
authors.forename: Maria
authors.initials: M
authors.lastname: Rodo
authors.forename: Hanna
authors.initials: H
authors.lastname: Wehr
authors.forename: Danuta Krystyna
authors.initials: DK
authors.lastname: Ryglewicz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D003704:Dementia / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human